Strong opioids (Fig. 9.5) are used in moderate to severe pain, particularly visceral, postoperative or cancer-related; in myocardial infarction and acute pulmonary oedema; and in perioperative analgesia (p. 146).

Fig. 9.5 Opioid analgesics

Weak opioids (Fig. 9.5) are used in the relief of ‘mild to moderate’ pain, as antitussives (Ch. 3) and as antidiarrhoeal agents (Ch. 8), taking advantage of these ‘side-effects’ of opioid analgesics.

Contraindications

Opioid analgesics should not be given to people in acute respiratory depression, with acute alcoholism, at risk of paralytic ileus, and with head injuries prior to neurological assessment (interferes with assessment of the level of consciousness).

Adverse effects

Opioid analgesics share many side-effects. These can be subdivided into central adverse actions and peripheral adverse actions.

Central adverse actions include the following:

• Drowsiness and sedation, in which initial excitement is followed by sedation and finally coma (on overdose)

• Reduction in sensitivity of the respiratory centre to carbon dioxide, leading to shallow and slow respiration

• Tolerance and dependence (Ch. 5)

• Suppression of cough, an effect exploited clinically in antitussives (Ch. 3)

• Vomiting due to stimulation of the chemoreceptor trigger zone (CTZ)

• Pupillary constriction due to stimulation of the parasympathetic third cranial nerve nucleus

• Hypotension and reduced cardiac output, which are partly due to reduced hypothalamic sympathetic outflow.

Peripheral adverse actions include the following:

• Constipation, is partly due to stimulation of cholinergic activity in gut wall ganglia which results in smooth wall spasm

• Contraction of smooth muscle in the sphincter of Oddi and in the ureters, which results in an increase in blood amylase and lipase due to pancreatic stasis

• Histamine release, which produces bronchospasm, flushing and arteriolar dilatation

• Lowered sympathetic discharge and direct arteriolar dilatation, which results in lowered cardiac output and hypotension.

Adverse effects of opioids tend to limit the dose that can be given, and the level of analgesia that can be maintained. The most serious of all these effects is respiratory depression, which is the most common cause of death from opioid overdose.

Constipation and nausea are also common problems and clinically it is common to co-administer laxatives and an antiemetic (Ch. 8).

Tolerance and dependence

Tolerance to opioid analgesics can be detected within 24–48 hours from the onset of administration, and it results in increased doses of the drug being needed to achieve the same clinical effect.

Dependence involves μ receptors and is both physical and psychological in nature and is discussed in Chapter 5. If physical dependence develops, it is characterized by a definite withdrawal syndrome following cessation of drug treatment. This syndrome comprises a complex mixture of irritable, and sometimes aggressive, behaviour combined with extremely unpleasant autonomic symptoms such as fever, sweating, yawning and pupillary dilatation. The withdrawal syndrome is relieved by the administration of μ receptor agonists, and worsened by the administration of μ receptor antagonists.

Psychological dependence of opioid analgesics is based on the positive reinforcement provided by euphoria.

In the clinical context, especially in terminal care, where tolerance and dependence can be monitored, they are not inevitably problematic. However, the fear of tolerance and dependence often leads to over-caution in the use of opioid analgesics, and inadequate pain control in some patients.